Anorexia nervosa is a disease characterized by severe loss of weight with increased morbidity. The disorder is associated with multiple severe medical consequences, resulting in the highest mortality rate among psychiatric disorders. The disorder represents an important public health concern, given its significant incidence among adolescents and young adults. Treatment strategies used to date have been largely ineffective and there is a critical need to develop and explore novel therapeutic paradigms. Psychiatric co-morbidities including anxiety and depressions are common in patients with anorexia nervosa. Studies have also shown that co- morbid anxiety and depressive symptoms are often associated with eating disorder persistence and outcome, and, that severe depression and higher levels of anxiety predict poor eating disorder outcome. We have shown that a previously unrecognized endocrine deficiency, low levels of the hormone testosterone is common in women with anorexia nervosa and directly related to disease severity. In preliminary data, physiologic testosterone replacement is associated with a reduction in Eating Disorders Inventory-2 scores, and increase in BMI and decreases in psychiatric co-morbidities. We hypothesize that testosterone is an effective means to reduce to major co-morbidities, depression and anxiety and in doing so will lead to an improvement in Eating Disorders Examination scores and overall improvement in core anorexia nervosa symptoms. The overall goal of this study is to determine the efficacy of low-dose testosterone replacement in the treatment of anorexia nervosa. This will be accomplished by physiologic testosterone administration through a novel transdermal delivery system. Patients will be randomized to either testosterone or a placebo patch. The main endpoints will be BMI, Eating Disorders Inventory-2 scores, depression and anxiety scores. The demonstration of testosterone efficacy in this population would represent a novel strategy to treating this disorder. PUBLIC HEALTH RELEVANCE: Anorexia nervosa is a disease with increased morbidity and has the highest mortality rate of any psychiatric disease and treatment strategies used to date have been largely ineffective. Low levels of the hormone testosterone occur in this disease and physiologic testosterone replacement is associated with a reduction core symptoms and associated morbidities. We propose to investigate whether long-term testosterone replacement improves symptoms of anorexia nervosa.